Medical device comprising a wetted hydrophilic coating

ABSTRACT

The invention is directed to the use of a wetting agent having a boiling point higher than 100° C. and a viscosity lower than 500 mPa.s, wherein the wetting agent comprises water in an amount between 0 and 4.9 wt % based on the total weight of the wetting agent, for the lubrication of a hydrophilic polymer coating. The invention further relates to a medical device comprising a hydrophilic polymer coating that is wetted by a wetting agent, a method for the preparation of a medical device and a package comprising a medical device.

The invention is directed to the use of a wetting agent having a boilingpoint higher than 100 ° C. and a viscosity lower than 500 mPa.s, whereinthe wetting agent can comprise water in an amount between 0 and 4.9 wt %based on the total weight of the wetting agent for the lubrication of ahydrophilic polymer coating. The invention further relates to a medicaldevice comprising a hydrophilic polymer coating that is wetted by awetting agent having boiling point higher than 100 ° C. and a viscositylower than 500 mPa.s, wherein the wetting agent can comprise water in anamount between 0 and 4.9 wt % based on the total weight of the wettingagent, a method for the preparation of a medical device and a packagecomprising a medical device.

Many medical devices, such as guide wires, urinary and cardiovascularcatheters, syringes, and membranes need to have a lubricant applied tothe outer and/or inner surface to facilitate insertion into and removalfrom the body and/or to facilitate drainage of fluids from the body.Lubricious properties are also required so as to minimize soft tissuedamage upon insertion or removal. Especially, for lubrication purposes,such medical devices may have a hydrophilic surface coating or layerwhich becomes lubricious and attains low-friction properties uponwetting, i.e. applying a wetting fluid for a certain time period priorto insertion of the device into the body of a patient. A coating orlayer which becomes lubricious after wetting is hereinafter referred toas a hydrophilic coating. A coating obtained after wetting ishereinafter referred to as a lubricious coating. Herein lubricious isdefined as having a smooth or slippery surface.

In the prior art the following wetting fluids are described; water,water-containing mixtures further comprising one or more organicsolvents and/or one or more dissolved components, such as salts.According to the prior art a wetting fluid can also be a body fluid or asaline solution having (approximately) physiological osmolarity.

In principle, the medical devices can be wetted (and thereby becomelubricious) immediately prior to use. However, from a user's point ofview it is desirable to be able to use the device directly after openingof the packaging wherein it is stored. In view of this, medical deviceswith a hydrophilic coating have been introduced that aresterile-packaged in a package that contains enough wetting fluid to keepthe coating wetted (and thus lubricious).

WO-0405909A1 discloses the use of plasticizers in a cross-linkedhydrophilic coating of a hydrophilic polymer on a substrate. Theplasticizers form part of the polymer solution that is applied to thesubstrate. After application the polymer solution is dried and cured.The substrate can be a medical device, such as a catheter, guide wire orendoscope. The medical devices that are coated with the hydrophiliccoating are wetted with water before use on a patient. The plasticizershave the effect that a hydrophilic coating is provided showing highabrasion resistance and low friction coefficient when wet.

EP-1809345A1 discloses a medical device having a wetted hydrophiliccoating comprising a coating composition containing a hydrophilicpolymer and a wetting agent comprising water and one or morelubricant(s). The wetting agent comprises one or more lubricants in atotal amount between 0.1 and 95% by weight. The medical devices have alow friction surface, have an extended dry-out period and do not drip orhave a reduced tendency to drip.

The above described hydrophilic coatings have the disadvantage thatwater is used for the lubrication of the hydrophilic coatings. By usingwater as the main component in a wetting agent the hydrophilic coatingwill dry out and will thus not be lubricous for a long time. Thehydrophilic coating will usually not be lubricous anymore within a timeperiod of 15 minutes after wetting or after removal of a medical devicefrom the package.

It has now surprisingly been discovered that a wetting agent having aboiling point higher than 100° C. and a viscosity lower than 500 mPa.s,wherein the wetting agent can comprise water in an amount between 0 and4.9 wt % based on the total weight of the wetting agent can be used forthe lubrication of a hydrophilic polymer coating on a substrate, whereafter the lubricious hydrophilic coating will stay lubricous for a timeperiod that is much longer than 15 minutes.

A further advantage is that the lubricious hydrophilic coatings do notdrip.

The wetting agent has a boiling point higher than 100° C., preferablyhigher than 200° C. The boiling point is determined at ambient pressure.

A high boiling point of the wetting agent corresponds to a low amount ofevaporation of the wetting agent from the lubricous hydrophilic coating.This means that the hydrophilic coating will remain lubricous for alonger time.

The wetting agent can be one liquid or a mixture of liquids. The wettingagent can comprise water, but only in a minor amount. The amount ofwater in the wetting agent is at most 4.9 weight % based on the totalweight of wetting agent. The amount of water preferably is lower than 4weight %, more preferably lower than 1 weight %.

The wetting agent has a viscosity lower than 500 mPa.s. This isdetermined by at a temperature of 25° C. on a viscometer according toASTM D445. The viscosity of water is 1 mPa.s. The viscosity of thewetting agent is preferably below 100 mPa.s. The viscosity of thewetting agent is preferably higher than 1 mPa.s; more preferably higherthan 5 mPa.s. A low viscosity of the wetting agent corresponds to a lowamount of friction between the lubricious hydrophilic coating andanother surface.

The wetting agent preferably comprises at least one hydroxyl group. Morepreferably, the wetting agent can be chosen from the group consisting ofglycerol esters, glycerol ethers, glycols, glycolesters andglycolethers. Examples of wetting agents are glycerol, monoacetin,diacetin and diacetone alcohol.

The wetting agents are used for the lubrication of a hydrophilic polymercoating. The hydrophilic coating may be any coating which comprises ahydrophilic medium that absorbs and/or adsorbs the wetting agent. Thiscan be any coating comprising hydrophilic polymers, an antimicrobialcoating, a non-fouling coating or a drug eluting coating.

A hydrophilic polymer coating comprises a hydrophilic polymer capable ofproviding hydrophilicity to the coating, which polymer may be syntheticor bio-derived and can be blends or copolymers of both. Suitablehydrophilic polymers include but are not limited to poly(lactams), forexample polyvinylpyrollidone (PVP), polyurethanes, homo- and copolymersof acrylic and methacrylic acid, polyvinyl alcohol, polyvinylethers,maleic anhydride based copolymers, polyesters, vinylamines,polyethyleneimines, polyethyleneoxides, poly(carboxylic acids),polyamides, polyanhydrides, polyphosphazenes, cellulosics, for examplemethyl cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, andhydroxypropylcellulose, heparin, dextran, polysacharrides, for examplechitosan, hyaluronic acid, alginates, gelatin, and chitin, polyesters,for example polylactides, polyglycolides, and polycaprolactones,polypeptides, for example collagen, fibrins, elastin, albumin, oligopeptides, polypeptides, short chain peptides, proteins, andoligonucleotides.

Preferably the hydrophilic polymer coating comprises poly(lactams), forexample polyvinylpyrollidone (PVP), polyurethanes, homo- and copolymersof acrylic and methacrylic acid, polyvinyl alcohol, polyvinylethers,maleic anhydride based copolymers, polyesters, vinylamines,polyethyleneimines or polyethyleneoxides.

More preferably the hydrophilic polymer coating comprisespolyvinylpyrrollidone (PVP).

Generally the hydrophilic polymer has a molecular weight in the range ofabout 8,000 to about 5,000,000 g/mol, preferably in the range of about20,000 to about 3,000,000 g/mol and more preferably in the range ofabout 200,000 to about 2,000,000 g/mol. The hydrophilic polymer may beused in the coating in more than 1 wt %, for example more than 5 wt %,or more than 50 wt %, based on the total weight of the dry coating. Thehydrophilic polymer can be present up to 99 wt %, or up to 95%, based onthe total weight of the dry coating.

The hydrophilic polymer may for instance be a prepolymer, i.e. a polymercomprising one or more polymerisable groups, in particular one or moreradically polymerisable groups such as one or more vinyl groups.

For providing a cross-linked network, a prepolymer having an averagenumber of polymerisable groups per molecule of more than 1 is inparticular suitable. Preferably, the average number of reactive groupsis at least 1.2, more preferably at least 1.5, in particular at least2.0. Preferably the average number of groups is up to 64, morepreferably in the range of up to 15, in particular in the range of up to8, more in particular up to 7.

However, also a hydrophilic polymer which is free of such polymerisablegroups may be cured in the presence of a photo-initiator, in particularby the formation of grafts when the formulation is exposed to light.

The hydrophilic coating composition may be in the form of a solution ora dispersion comprising a liquid medium. Herein any liquid medium thatallows application of the hydrophilic coating formulation on a surfacewould suffice. Examples of liquid media are alcohols, like methanol,ethanol, propanol, butanol or respective isomers and aqueous mixturesthereof or acetone, methylethyl ketone, tetrahydrofuran,dichloromethane, toluene, and aqueous mixtures or emulsions thereof.

The hydrophilic coating composition according to the invention mayadditionally include various additives includes conventional ingredientslike pigments, dyes, dispersing and stabilising agents (usuallysurfactants or emulsifiers), rheology control agents, flow-promotingagents, extenders, defoaming agents, plasticisers, thickeners, heatstabilisers, levelling agents, anti-cratering agents, fillers,sedimentation inhibitors, UV absorbers, antioxidants, organicco-solvents, wetting agents, fungicides, bacteriocides, anti-freezeagents, coalescents, waxes and the like introduced at any stage of theproduction process or subsequently.

The hydrophilic coating can be coated on a substrate which may beselected from a range of geometries and materials. The substrate mayhave a texture, such as porous, non-porous, smooth, rough, even oruneven. The substrate supports the hydrophilic coating on its surface.The hydrophilic coating can be on all areas of the substrate or onselected areas. The hydrophilic coating can be applied to a variety ofphysical forms, including films, sheets, rods, tubes, molded parts(regular or irregular shape), fibers, fabrics, and particulates.Suitable surfaces are surfaces that provide the desired properties suchas porosity, hydrophobicity, hydrophilicity, colorisability, strength,flexibility, permeability, elongation, abrasion resistance and tearresistance. Examples of suitable surfaces are for instance surfaces thatconsist of or comprise metals, plastics, ceramics, glass and/orcomposites. The hydrophilic coating may be applied directly to the saidsurfaces or may be applied to a pretreated or coated surface. Thepretreatment or coating can be designed to aid adhesion of thehydrophilic coating to the substrate.

Preferably, the hydrophilic polymer coating is coated on a medicaldevice. The medical device can be an implantable device or anextracorporeal device. The devices can be of short-term temporary use orof long-term permanent implantation. In certain embodiments, suitabledevices are those that are typically used to provide for medical therapyand/or diagnostics in heart rhythm disorders, heart failure, valvedisease, vascular disease, diabetes, neurological diseases anddisorders, orthopedics, neurosurgery, oncology, ophthalmology, and ENTsurgery.

Suitable examples of medical devices include, but are not limited to, astent, stent graft, anastomotic connector, synthetic patch, lead,electrode, needle, guide wire, catheter, sensor, surgical instrument,angioplasty balloon, wound drain, shunt, tubing, infusion sleeve,urethral insert, pellet, implant, blood oxygenator, pump, vasculargraft, vascular access port, heart valve, annuloplasty ring, suture,surgical clip, surgical staple, pacemaker, implantable defibrillator,neurostimulator, orthopedic device, cerebrospinal fluid shunt,implantable drug pump, spinal cage, artificial disc, replacement devicefor nucleus pulposus, ear tube, intraocular lens and any tubing used inminimally invasive surgery.

Devices that are particularly suited to be used in the present inventioninclude medical devices or components such as catheters, for exampleintermittent catheters, guidewires, stents, syringes, metal and plasticimplants, contact lenses and medical tubing.

The hydrophilic polymer coating can be applied to the substrate by forexample dip-coating. Other methods of application include spray, wash,vapor deposition, brush, roller and other methods known in the art.

The hydrophilic polymer coating may have one or more layers. One layermay be a primer layer useful for attaching the coating layer to themedical device.

The invention is further related to a method for the preparation of amedical device comprising the steps of:

-   -   providing a medical device that is at least partially coated        with a hydrophilic polymer coating,    -   providing a wetting agent with a boiling point higher than        100° C. and a viscosity lower than 500 mPa.s, wherein the        wetting agent can comprise water in an amount between 0 and 4.9        wt % based on the total weight of the wetting agent,    -   contacting the part of the medical device that is coated with        the hydrophilic polymer coating with the wetting agent in such a        way that the hydrophilic coating is lubricated by the wetting        agent,    -   optionally, sterilizing the medical device.

The hydrophilic polymer coating on the medical device must be wetted bythe wetting agent. The term “wetted” is generally known in the artand—in a broad sense—means “containing a wetting agent”. In particularthe term is used herein to describe a coating that contains sufficientwetting agent to be lubricious. A lubricious coating has a Coefficientof Friction (COF), as defined below, lower than 0.15. In terms of theconcentration of the wetting agent, usually a wetted coating contains atleast 10 wt. % of wetting agent, based on the dry weight of the coating,preferably at least 50 wt. %, based on the dry weight of the coating,more preferably at least 100 wt. % based on the dry weight of thecoating. For instance, in a particular embodiment of the invention anuptake of wetting agent of about 300-500 wt. % is feasible.

Preferably, a lubricious coating is obtained with a dry-out time longerthan 15 minutes as determined on the Harland Friction tester. Within thecontext of the invention, the dry-out time is the duration of thecoating remaining lubricious after the device has been taken out of thewetting agent wherein it has been stored and wetted or after the devicehas been taken out of the package wherein it has been stored in a wettedcondition. Dry-out time can be determined by measuring the coefficientof friction as a function of time the catheter had been exposed to airon the Harland Friction tester. The dry-out time is the point in timewherein the coefficient of friction reaches a value of 0.2 or higher, orin a stricter test 0.15 or higher. The protocol is as indicated in theExamples.

Preferably, a lubricious hydrophilic coating is obtained with acoefficient of friction lower than 0.20 as determined on the HarlandFriction tester. A coating is considered lubricious if it has a frictionas measured on a Harland FTS Friction Tester of 0.20 or less at aclamp-force of 100 g and a pull speed of 1 cm/s, preferably of 0.15 orless. The protocol is as indicated in the Examples.

Optionally, the medical device is sterilized. Sterilization can beachieved by applying the proper combinations of heat, chemicals and/orirradiation.

Heat sterilization can be performed in an autoclave, wherein steam isheated to 120-135° C. During chemical sterilization the medical deviceis for instance contacted with ethylene oxide (EtO), ozone or hydrogenperoxide. Sterilization by irradiation can, for instance, be performedby electron beam, x-ray or gamma ray irradiation.

The hydrophilic coating and or the wetting agent may comprise additivesthat protect the coating against a detrimental effect of radicals formedduring sterilization. These additives are for example aliphaticcompounds, alicyclic compounds and/or antioxidants.

In principle any aliphatic stabilising compound and/or alicyclicstabilising compound may be used, in particular any such compound thatis physiologically allowable and preferably non-toxic in the usedconcentration.

A stabilising compound with a relatively low molecular weight isparticularly suitable, such as a compound with a molecular weight ofless than 1000 g/mol, more in particular of 800 g/mol or less,preferably of 600 gram/mol or less. The use of a low molecular weightcompound may have one or more of the following advantages, compared to acompound having a higher molecular weight:

Particularly preferred aliphatic and/or alicyclic stabilising compoundsinclude alcohols, ethers, aldehydes, ketones, amides, esters, thiols,thioesters, organic acids and combinations thereof. Highly preferred are(saturated) aliphatic compounds selected from the group consisting of(saturated) aliphatic alcohols, ethers, aldehydes, ketones amides,esters, thiols, thioesters, organic acids and combinations thereof.

Preferred alcohols include alkylene glycols, such as diethyleneglycol,triethyleneglycol, tetraethyleneglycol, propyleneglycol,dipropyleneglycol, triprolyeneglycol, (low molecular) ethoxylated orpropoxylated alcohols and/or amines like ethanolamine, diethanolamine,triethanolamine, polyethylene glycol (PEG), in particular polyalkyleneglycols having a Mw up to about 600 g/mol lower aliphatic alcohols—inparticular C1-C8 alcohols, more in particular C2-C4 alcohol, such asisopropanol, ethanol, 1-propanol and 1-butanol—and combinations thereof.Good results have further been achieved with a carbohydrate, inparticular a monosaccharide, more in particular glucose.

Preferred ethers include polyalkylene glycols, such as PEG.

Suitable aldehydes include C1-C8 aldehydes. Preferred aldehydes includeformaldehyde, acetaldehyde and butanal.

Suitable ketones include C3-C8 ketones. Preferred ketones includeacetone and methylethylketone.

Suitable organic acids include C1-C8 organic acids. Preferred organicacids include formic acid.

The invention is further directed to a package containing a medicaldevice or a part of a medical device comprising a lubricated hydrophiliccoating, which package is impermeable to vapor. The package can, forinstance, be made of plastic or aluminum foil. The package can containadditional wetting agent.

Preferably, the package comprises a medical device that is sterilized.

The invention will now be illustrated by the following, non-limitingexamples.

EXAMPLES 1-5 AND COMPARATIVE EXPERIMENT A-H Primer Coating Formulation

The primer formulation was prepared by dissolving the components belowin ethanol.

-   PTGL1000(T-H)₂oligomer: 4.25% (w/w)-   PVP K85 (supplied by BASF): 0.75% (w/w)-   Irgacure 2959 (supplied by Sigma Aldrich): 0.20% (w/w)-   Ethanol 96% (supplied by Merck): 94.8% (w/w)

The synthesis of PTGL1000(T-H)₂ oligomer is described in W02007/065722.

Hydrophilic Coating Formulation

The hydrophilic coating formulation was prepared by dissolving thecomponents below in a water/ethanol mixture 1:1 based on weight.

Weight %

-   PVP K85: 5.20-   Polyacrylamide-co-acrylic acid sodium salt (PAcA): 0.35 (supplied by    Sigma Aldrich)-   Irgacure 2959 (supplied by Sigma Aldrich): 1-   Benzophenone: 1-   Ethanol (96%): 47.45-   Water: 45

Coating Application

PVC tubes with a diameter of 14 Fr and a length of 30 cm were coated ona Harland PCX coater 175/24.

The PVC tubes were first dip-coated with the primer coating formulationand cured according the dip protocol for the primer in table 1.Subsequently the hydrophilic coating formulation was applied and curedaccording the dip protocol for the hydrophilic coating. Temperature andhumidity during application were respectively 21° C. +/−2° C. and 40%+/−15%.

The Harland PCX coater/175/24 was equipped with a Harland Medicalsystems UVM 400 lamp. Intensity of the lamps of the Harland PCXcoater/175/24 was on average 60 mW/cm² and was measured using a SolatellSola Sensor 1 equipped with an International Light detector SED005#989,Input Optic: W#11521, filter: wbs320#27794. The IL1400A instructionmanual of International Light was applied, which is available on theInternet: www.intl-light.com. For the applied parameters in the PCXcoater see Table 1.

The tubes were dipped in the wetting agent, immersed for 2 minutes andthereafter extracted from the wetting agent with a speed of 1 cm/s. Thewetted coatings were evaluated directly after removal from the wettingagent.

All measurements were performed at a relative humidity of 40-50%.

TABLE 1 Applied parameters in the PCX Coater Coating parametersselection table Primer Hydrophilic coating coating Dipping Cycle Movedevice carrier to position (cm) 125 125 Speed (cm/sec) 6.5 6.5accelaration (sec) 0.1 0.1 Move device carrier down (cm) 11.5 11.5 speed(cm/sec) 4 2 accelaration (sec) 0.1 0.1 Move device carrier down (cm)27.5 27.5 speed (cm/sec) 2 2 accelaration (sec) 0.1 0.1 Time Pause (sec)10 10 Move device carrier up (cm) 28.5 28.5 speed (cm/sec) 1 1accelaration (sec) 0.1 0.1 Move device carrier to position (cm) 148 148speed (cm/sec) 6.5 6.5 accelaration (sec) 0.1 0.1 Cure Cycle Rotator On(rpm) 2 2 UV lights Full Power Drying time (sec) 90 90 Time pause (sec)30 Varied: 180, 240 or 360 Close Shutter UV lights Standby Power RotatorOffTest methodsViscosity test

The viscosity of a wetting agent was determined on a viscometeraccording to ASTM D445 at a temperature of 25° C.

Lubricity Test

Lubricity tests were performed on a Harland FTS5000 Friction Tester(HFT). The protocol was selected: see Table 2 for HFT settings. Frictiontester pads were used from Harland Medical Systems, P/N 102692, FTS5000Friction Tester Pads, 0,125*0,5**0,125, 60 durometer.

Subsequently the desired test description was inserted when “run test”was activated. A sample was fastened in the sample holder.. Thetransport of the tester was moved to the desired position and theprotocol was activated by pushing “start”. The data were saved afterfinishing. The sample holder was removed from the tester andsubsequently the catheter was removed from the holder.

TABLE 2 HFT settings Transport movement (cm) 10 Clamp force (g) 100 Pullspeed (cm/s) 1 Acceleration time (s) 2

The measured coefficient of friction (COF) is used to rate theperformance of the coating. The COF is defined as the measuredfriction\clamp force. The COF was determined on a sample after 10, 15and 30 minutes of drying. The drying time started directly after removalof the sample from the wetting agent.

A COF<0.15 is judged as good. A COF between 0.15 and 0.20 is judged astoo high; a COF>0.20 is judged as bad.

TABLE 3 Results of the lubricity test Boiling Viscosity Point (mPa · sCOF COF COF Wetting Agent (° C.) @ 25° C.) (10 min) (15 min) (30 min)Example 1 diacetone alcohol 168 0.34 0.22 >0.5 — 2 monoacetin 253 400.09 0.09 0.09 3 Diacetin 259 45 0.11 0.11 0.11 4 Propyleneglycol 188 400.07 0.06 0.06 5 triacetin 260 23 >0.5 — — Comparative Experiment Awater 100 1 0.02 >0.5 — B Glycerol 290 934 0.25 0.22 0.19 CDiacetin/water 105 1.6 0.16 0.40 — 10 wt %/90 wt % D Diacetin/water 12012 0.16 0.4 0.8  50 wt %/50 wt % E Diacetin/water 209 31 0.10 0.15 — 90wt %/10 wt % F Propyleneglycol/water 102 1.2 0.12 0.8 — 10 wt %/90 wt %G Propyleneglycol/water 109 10 0.16 0.27 — 50 wt %/50 wt % HPropyleneglycol/water 130 29 0.08 0.10 — 90 wt %/10 wt %

The results obtained with triacetin show a high COF. It was observedthat this compound was absorbed insufficiently by the coating.

The results obtained with mono- and diacetin show a low friction valuethat remained unchanged over the whole test period of 30 minutes. Evenafter remeasuring the samples after 16 hours in air almost no change infriction was observed (COF was 0.12).

Comparative experiments C-F show that the addition of water to thewetting agent shortens the time that a coating remains lubricious afterthe removal of the wetted coating from the wetting agent.

1.-13. (canceled)
 14. A package comprising a medical device, the medicaldevice comprising: a hydrophilic polymer coating that is wetted by awetting agent having a boiling point higher than 100° C. and a viscositylower than 500 mPa.s, wherein the wetting agent comprises water in anamount between 0 and 4.9 wt % based on the total weight of the wettingagent, wherein the package is impermeable to vapor, and wherein themedical device is sterilized.
 15. The package according to claim 14,wherein the wetting agent comprises at least one hydroxyl group.
 16. Thepackage according to claim 14, wherein the wetting agent is chosen fromthe group consisting of glycerol esters, glycerol ethers, glycols,glycolesters and glycolethers.
 17. The package according to claim 14,wherein the hydrophilic polymer coating is crosslinked.
 18. The packageaccording to claim 14, wherein the hydrophilic polymer coating comprisespolyvinylpyrrollidone (PVP).
 19. The package according to claim 14,wherein the dry-out time of the hydrophilic polymer coating is longerthan 15 minutes as determined on a Harland Friction tester.
 20. Thepackage according to claim 14, wherein the hydrophilic polymer coatinghas a coefficient of friction lower than 0.2 as determined on a HarlandFriction tester.
 21. The package according to claim 14, wherein themedical device is sterilized by applying electron beam, x-ray or gammaray irradiation.
 22. The package according to claim 14, wherein thewetting agent comprises a member of the group consisting of glycerol,monoacetin, diacetin and diacetone alcohol.
 23. The package according toclaim 14, wherein the wetting agent comprises propyleneglycol.
 24. Thepackage according to claim 14, wherein the wetting agent consists ofpropyleneglycol.
 25. The package according to claim 14, wherein thewetting agent further comprises a stabilizing compound.
 26. The packageaccording to claim 14, wherein the wetting agent comprises an alkylenealcohol.
 27. The package according to claim 14, wherein the wettingagent comprises a member of the group consisting of diethyleneglycol,triethyleneglycol, tetraethyleneglycol, propyleneglycol,dipropyleneglycol, triprolyeneglycol, ethanolamine, diethanolamine,triethanolamine, and polyethylene glycol.
 28. The package according toclaim 14, wherein the wetting agent comprises a polyalkylene glycol. 29.The package according to claim 23, wherein the medical device issterilized by applying electron beam, x-ray or gamma ray irradiation.30. The package according to claim 24, wherein the medical device issterilized by applying electron beam, x-ray or gamma ray irradiation.31. The package according to claim 27, wherein the medical device issterilized by applying electron beam, x-ray or gamma ray irradiation.32. The package according to claim 28, wherein the medical device issterilized by applying electron beam, x-ray or gamma ray irradiation.33. A method for the preparation of a medical device comprising thesteps of: (a) providing a medical device that is at least partiallycoated with a hydrophilic polymer coating, (b) providing a wetting agentwith a boiling point higher than 100° C. and a viscosity lower than 500mPa.s, wherein the wetting agent comprises water in an amount between 0and 4.9 wt % based on the total weight of the wetting agent, (c)contacting the part of the medical device that is coated with thehydrophilic polymer coating with the wetting agent in such a way thatthe hydrophilic coating is lubricated by the wetting agent, and (d)sterilizing the medical device.